“Etomidate”, ethyl R-(+)-1-(1-phenethyl)-1H-imidazole-5-carboxylate, is an intravenous anesthetic drug with the characteristics of rapid onset, short duration of action, quick recovery, and slight inhibition to cardiovascular and respiratory systems. In clinical, etomidate is mainly used in anesthesia induction, and anesthesia for clinical surgery. The structure of etomidate is as follows:

However, researches have shown that while exerting the anesthetic effect, etomidate may have an inhibitory effect on 11β-hydroxylase, and thereby reduce the secretion of cortisol and/or corticosterone. Hence, there is a potential fatal risk in long term application of etomidate.
Extensive studies have been done by pharmaceutical chemists to overcome the disadvantages of etomidate and develop novel drugs which possess the advantages of etomidate without inhibiting the secretion of cortisol and/or corticosterone as strongly as etomidate. For example, Cotten J F et al. (Methoxycarbonyl-etomidate: A novel rapidly metabolized and ultra-short-acting etomidate analogue that does not produce prolonged adrenocortical suppression, Anesthesiology, 2009, 111: 240-9) reported an etomidate derivative of Formula 7, which shows a lower inhibitory effect on the secretion of cortisol and/or corticosterone, but has a drastically decreased anesthetic effect in the meantime. Similarly, Laha, Joydev K et al. (Synthesis of Fused Imidazoles, Pyrroles, and Indoles with a Defined Stereocenter α to Nitrogen Utilizing Mitsunobu Alkylation Followed by Palladium-Catalyzed Cyclization, Journal of Organic Chemistry, 2011, vol. 76, #20, p 8477-8482) disclosed a Carboetomidate-type etomidate derivative of Formula 8, which has little inhibition to the secretion of cortisol and/or corticosterone, but has decreased anesthetic activity and prolonged duration of action in the meantime.

In view of the above problems, it has great practical significance to develop an etomidate derivative having both favorable anesthetic effect and safety profiles.